Cognitive dysfunction is common in patients with autoimmune disorders such as systemic lupus erythematosus (SLE). These deficits can impact a wide range of activities and a better understanding of the nature and pathogenesis is critical to developing effective treatment approaches in these patients. Despite many prior investigations into autoimmune and vascular abnormalities associated with brain dysfunction in SLE, no one specific underlying mechanism has emerged. SLE is a multi-organ disease and pulmonary involvement has been identified in up to 60% of SLE patients. In a small sample of SLE subjects we found unexpected pulmonary abnormalities related to cognitive dysfunction and our first aim in this study is to compare lung function and exercise capacity in a larger cohort of SLE and control subjects, and evaluate the relationship between lung function, exercise capacity and cognition. The model is based on prior studies in patients with chronic obstructive pulmonary disease (COPD) where cognitive deficits have been associated with poor lung function, exercise capacity and depression. Given the heterogeneity of SLE manifestations we will minimize diversity in some factors (i.e. age, length of diagnosis, disease severity and medication use). We also aim to evaluate and validate the use of brief self-report measures of exercise that are easy to obtain, applicable and valid for this population. This will allow development of larger, cost-effective treatment protocols for future investigations. Finally, we aim to examine whether or not exercise improves cognitive function in a small sample of mildly diseased middle aged SLE patients with established disease duration. If improvement is noted we will explore predictors common to other populations (i.e. lung function, exercise capacity and depression) as well as factors specific to autoimmune SLE disease characteristics as mechanisms of change. Ultimately, we aim to use this pilot study to evaluate the feasibility and utility of cardiopulmonary exercise as an intervention and to guide the design of larger trials that will examine the effectiveness of such an intervention in treating cognitive dysfunction in patients with SLE and possibly other rheumatic autoimmune disorders. PUBLIC HEALTH RELEVANCE: Cognitive dysfunction in patients with systemic lupus erythematosus (SLE) is common, and yet mechanisms remain unclear and treatment options limited. This pilot study will investigate basic pulmonary problems and/or exercise limitations contributing to cognitive dysfunction in SLE. It will also examine whether an exercise program for this group is feasible and demonstrates improvement on cognitive ability. Developing novel treatments for cognitive dysfunction in SLE could have positive effects for public health in these and other autoimmune patients.